Project Summary Brian Haas is an accomplished Senior Computational Biologist and bioinformatics programmer at the Broad Institute who contributes to many cancer research activities under the mentorship of Unit Director Aviv Regev. He has developed several very popular open-source bioinformatics software tools to support genome and transcriptome studies, and has authored or co-authored dozens of manuscripts in leading scientific journals. For more than 15 years, he has leveraged genome and transcriptome analyses to gain insights into the biology of diverse organisms, including pathogens, animal vectors of disease, and most recently cancer. He played a critical role in developing the NCI-funded Trinity Cancer Transcriptome Analysis Toolkit, a suite of software that uses RNA-Seq data to capture cancer mutations, fusion transcripts, evidence of aberrant splicing and expression, and exploration of tumor heterogeneity through single cell transcriptome analysis. In this NCI R50 proposal, we propose salary support for Haas under Regev's mentorship, to support him in (1) continuing to develop open-source software for use by the cancer research community, (2) integrating these tools into NCI-supported infrastructures including the NCI Cloud to maximize accessibility and impact, (3) applying these tools to large collections of cancer transcriptome data made available via TCGA and other large-scale efforts, and (4) making the resulting findings available as companion resources to these efforts. Based on his past contributions to bioinformatics and scientific research and the support he has gained from the Broad Institute cancer research programs and abroad, we believe Haas will be tremendously successful as a NCI Cancer Research Specialist.